AB0158 GENETIC EVIDENCE OF CASUAL ASSOCIATION BETWEEN POLYMYOSITIS AND RISK OF INTERSTITIAL LUNG DISEASE: A MENDELIAN RANDOMIZATION STUDY
Authors: Z. J. Yuan, R. Zhao, M. K. Yao, J. Y. Li, S. Y. Liu Yue, S. X. Zhang, X. Li, C. Wang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Polymyositis (PM) is an immunologically abnormal inflammatory myopathy, which is one of the common types of idiopathic inflammatory myopathy<sup>[1]</sup>. A global prevalence of approximately 41% of Interstitial lung disease (ILD) in PM patients has been estimated, which causes significant morbidity and mortality<sup>[2]</sup>. There have been a number of studies shown that PM and ILD may have similar pathogenesis, which focus on PM may induce ILD cellular immune system components<sup>[3]</sup>. While the two diseases may occur at the same time, but there is no directly evidence that the two diseases are causally related. <h3>Objectives</h3> Our study aimed to discover the casual association between PM and ILD, and determine the impact of PM on ILD. <h3>Methods</h3> We retrieved two large European genome-wide association study (GWAS) summary data of PM and ILD from MRC IEU OpenGWAS, which included 213,264 and 218,072 individuals, respectively. Single-nucleotide polymorphisms (SNPs) linked with disease were selected as instrumental variables (IVs) using genome-wide significance levels (P &lt; 1.0 × 10<sup>-5</sup>). And the interference of confounding factors, including smoking, drinking and BMI were eliminated. The two-sample Mendelian randomization (MR) method was applied to estimate the casual relationship of PM on ILD. The random-effects inverse variance weighted method (IVW) was mainly used to the MR analysis. Additionally, the horizontal pleiotropy effect was analyzed by MR-Egger and weighted median method sensitivity test. A leave-one-out analysis was conducted to avoid bias caused by a single SNP. <h3>Results</h3> Our study discovered that PM was considered as a risk factor of ILD. 15 SNPs strongly associated with PM were extracted from GWAS. The existence of PM may increase the risk of ILD by 1% (OR = 1.008, 95% CI: 1.001 - 1.016, p = 0.002) No single SNP significantly biased the causal effect of PM on ILD (Q = 0.18). No significant directional horizontal pleiotropy between PM and ILD was presented in the MR-Egger regression analysis. <h3>Conclusion</h3> This study provides evidence of an adverse effect of PM on ILD. And these may be meaningful for the prevention and intervention of PM and ILD. Meanwhile, our work also provides genetic statistical evidence for the study of the causal relationship of PM and ILD. <h3>References</h3> [1]Lundberg IE, Fujimoto M, Vencovsky J, et al. Idiopathic inflammatory myopathies. <i>Nature reviews Disease primers</i> 2021;7(1):86. doi: 10.1038/s41572-021-00321-x [published Online First: 2021/12/04] [2]Sun KY, Fan Y, Wang YX, et al. Prevalence of interstitial lung disease in polymyositis and dermatomyositis: A meta-analysis from 2000 to 2020. <i>Seminars in arthritis and rheumatism</i> 2021;51(1):175-91. doi: 10.1016/j.semarthrit.2020.11.009 [published Online First: 2021/01/01] [3]Zhang L, Wu G, Gao D, et al. Factors Associated with Interstitial Lung Disease in Patients with Polymyositis and Dermatomyositis: A Systematic Review and Meta-Analysis. <i>PLoS One</i> 2016;11(5):e0155381. doi: 10.1371/journal.pone.0155381 [published Online First: 2016/05/14] <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.